Endovascular implantable bodies are used in medical technology, inter alia, for supporting vascular structures. In particular, endovascular prostheses and/or implants, in particular, endovascular stents, are used to treat coronary heart disease, in particular, acute myocardial infarction. Such bodies are also known for the treatment of aneurysms. Stents fundamentally have a support structure which is capable of supporting the wall of a vessel and widening the vessel and/or bypassing an aneurysm.
For this purpose, stents are inserted in a compressed state into the vessel and then expanded at the location to be treated and pressed against the vascular wall. This expansion may be performed with the aid of a balloon catheter, for example. Alternatively, self-expanding stents are also known. These are constructed from a superelastic metal, such as Nitinol.
However, extremely small injuries and cracks (dissections) arise in the vascular wall with the expansion of the blood vessel, which frequently heal without problems, but may result in approximately one-third of the cases in growths (proliferation) and finally in renewed vascular constriction (restenosis) due to the triggered cell growth. The expansion of the vessel by endovascular stents additionally does not remove the causes of the original stenosis, i.e., the molecular pathological changes in the vascular wall. One cause of restenosis is also the excess elasticity of the blood vessels stretched by the stent. The stretched blood vessel typically constricts excessively after removal of the balloon, so that the vascular cross-section is decreased in relation to the area of the blood vessel which was not stretched (obstruction, so-called negative remodeling). The latter effect may be avoided by the placement of an endovascular implant, typically a stent.
The introduction of stents into interventional treatment of stable and unstable angina pectoris in coronary heart diseases has resulted in a significant reduction of the rate of restenosis and thus in better long-term results, which is primarily to be attributed to the lumen acquisition, however, the extremely small injuries which occur, which may induce the proliferation, may in turn trigger a restenosis. In addition, the presence of a foreign body of this type in the vascular system may initiate a cascade of cellular molecular processes, which may result in a gradual overgrowth of the vessel (in particular also thrombosis) in the area in which the implant, in particular the stent, is implanted.
For some years, attempts have therefore been made to reduce the danger of restenosis upon the implantation of stents further by using stents coated with agents (local drug delivery (LDD); drug eluting stents (DES)). However, agent carriers which are implanted in vessels are also used in illnesses which are not coronary-related (drug reservoirs for non-coronary applications (cancer treatment, etc.)).
The carriers of agent-containing coating systems of this type typically consist of a biocompatible material which is either of natural origin or may be obtained synthetically. Numerous methods have been developed for applying the coating systems to the stent, such as rotation pulverization methods, immersion methods, and spraying methods. The coating system at least regionally covers the surface of the stent, a release of the pharmacological agent into the human or animal body occurring through gradual degradation of the carrier and/or diffusion into the surrounding tissue.
An agent-containing coating of endovascular stents is typically to be understood as a flat coating. However, the coatings may also partially comprise the existing holes and/or cavities of the stent geometry being filled or single-sided or punctual coatings existing on the support structure of the stent. Such coatings are, however, very technologically demanding and also time-consuming and costly. It has now been established that not all coating materials may be coated with and without incorporated agent(s) directly on the implantable body according to the typically used methods.
In general, in most coating methods prior dissolving of the polymer matrix is necessary before the coating. However, to ensure the necessary freedom from solvent of the “drug eluting” implant, sometimes complex method steps must be performed to extract the same solvent, which are performed after the coating step.
Because of differing physical-chemical properties of substrate surface and coating material (hydrophobic, hydrophilic properties), the desired surface properties of the implant to be produced may possibly not be achieved. To still achieve these properties, though, sometimes complex method steps are required for pretreating the particular surface, which may possibly also have consequences for the biocompatibility because of an additional manufacturing step.
Agent-charged polymer layers having a high agent charge may also in particular result in mechanical problems of the layer upon the dilation of the stent.
In the known coating forms of stents, one is typically restricted to one agent-dose combination, because it is very difficult to implement coatings which have different elution rates of an agent or elutions of multiple agents (multiple drug release, in particular dual-drug release, triple-drug release, etc.), in particular at different elution rates.